The phox2b gene encodes a transcription factor that is expressed in the developing enteric nervous system (ENS). An enhancer element has been identified in the zebrafish phox2b locus that can drive tissue specific expression of reporter genes in enteric neuron precursor cells. We have generated a transgenic zebrafish line in which the Kaede fluorescent protein is under the control of this phox2b enhancer. This line has stable expression of the Kaede protein in enteric neuron precursor cells over 3 generations. To demonstrate the utility of this line we compared the migration and division rates of enteric neuron precursor cells in wild type and the zebrafish ENS mutant lessen.
In a study of a large family with history of HSCR, we identified variants in LRBA, RET, the gene encoding the RET ligand (GDNF), IHH, and a gene encoding a mediator of IHH signaling (GLI3). These variants altered functions of the gene products when expressed in cells and knockout of ihh reduced the number of enteric neurons in the zebrafish gut.
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